Skin care compositions comprising substituted monoamines

ABSTRACT

Skin care compositions comprising certain substituted monoamines, which are particularly beneficial for skin lightening and achieving evenness of color, especially for face and underarm skin.

TECHNICAL FIELD

The present invention relates to compositions for face and body skin.

BACKGROUND OF THE INVENTION

The desire to look young and healthy is universal. The primaryattributes of the young and healthy-looking skin are evenness of theskin color and texture. Age spots and other skin hyperpigmentation areundesirable. In many parts of the world, consumers also want to lightentheir background skin color. Accordingly, there is a need forcommercially feasible, effective skin care compositions, especially skinlightening products.

Various compositions comprising some substituted monoamines or relatedstructures have been described, for example in EP 2193779 (Cognis); WO2005/016895 (KIM); WO 2008/009860 (L'Oreal); Hirota et al., U.S. Pat.No. 4,412,943; EP 0653208 (Pfizer, Inc.); Dowell et al., U.S. Pat. No.5,393,519; Winchell et al., US 2001/0041170; Chassot et al., US2003/0172471; DE 20110356 (Wella AG); Walton, US 2005/0220832; Wagner etal., US 2009/0010860; WO 2008/101692 (Beiersdorf AG); WO 2008/129188(L'Oreal); EP 0922 447 (Beiersdorf AG).

SUMMARY OF THE INVENTION

The present invention is based at least in part on the finding thatamong hundreds of compounds described as “substituted monoamines,” asub-group (Structure I below) with critical structural elements, iseffective at inhibiting melanin production.

The invention includes skin care compositions, preferably skinlightening compositions, comprising substituted monoamines of StructureI. The invention also includes methods of using such compositions forskin care, especially face and underarms, most especially for skinlightening.

DETAILED DESCRIPTION OF THE INVENTION

Except in the examples, or where otherwise explicitly indicated, allnumbers in this description indicating amounts of material or conditionsof reaction, physical properties of materials and/or use are to beunderstood as modified by the word “about.” All amounts are by weight ofthe final composition, unless otherwise specified.

It should be noted that in specifying any range of concentration oramount, any particular upper concentration can be associated with anyparticular lower concentration or amount.

For the avoidance of doubt, the word “comprising” is intended to mean“including” but not necessarily “consisting of” or “composed of.” Inother words, the listed steps or options need not be exhaustive.

The disclosure of the invention as found herein is to be considered tocover all embodiments as found in the claims as being multiply dependentupon each other irrespective of the fact that claims may be foundwithout multiple dependency or redundancy.

“Skin Care Composition” as used herein, is meant to include acomposition for topical application to skin of mammals, especiallyhumans. Such a composition may be generally classified as leave-on orrinse off, and includes any product applied to a human body forimproving appearance, cleansing, odor control or general aesthetics. Thecomposition of the present invention can be in the form of a liquid,lotion, cream, foam, scrub, gel, soap bar or toner, or applied with animplement or via a face mask, pad or patch. Non-limiting examples ofskin care compositions include leave-on skin lotions and creams,shampoos, conditioners, shower gels, toilet bars, antiperspirants,deodorants, dental products, shave creams, depilatories, lipsticks,foundations, mascara, sunless tanners and sunscreen lotions. “Skin” asused herein is meant to include skin on the face and body (e.g., neck,chest, back, arms, underarms, hands, legs, buttocks and scalp). Theinventive compositions are especially useful for application to skinareas with the highest incidence of hyperpigmentation—face andunderarms, most preferably the inventive compositions are skinlightening compositions, deodorants and anti-perspirants.

“Lightening” as used herein, means the lightening of skin color as wellas the lightening of spots (hyperpigmentation) on the skin, like agespots and freckles.

Substituted Monoamines

The inventive compositions include substituted monoamines of StructureI:

wherein R₁ is selected from the group consisting of cyclohexyl, phenyl,mono- and di-substituted phenyl with the following substituents: C₁-C₅alkyl, C₁-C₅ alkoxy, phenoxy; and R2 is hydrogen or methyl. Preferably,to achieve improved inhibition of melanin production R₁ is mono- ordi-substituted phenyl substituted, with one or two substitutionsindependently selected from the group consisting of hydrogen, methyl,ethyl, methoxy and phenoxy; and R₂ is selected from the group consistingof hydrogen and methyl.

It will be understood that Structure I also encompasses amine salts(e.g., halogen salts, tosylates, mesylates, carboxylates, andhydroxides).

Amounts of the substituted monoamines may range from 0.001% to 20%,preferably from 0.01 to 10%, more preferably from 0.1 to about 10%,optimally from 0.1to about 5% by weight of the composition.

Process of Making Substituted Monoamines

Reagents & Analytical Methods

All reagents and solvents were obtained from commercial sources(Sigma-Aldrich, EMD Chemicals) and used without further purificationunless otherwise indicated. Parallel reactions and parallel solventremoval were performed using a Buchi Syncore reactor (Buchi Corporation,New Castle, Del.). Reaction monitoring was performed using thin layerchromatography (TLC). TLC was performed using silica gel 60 F₂₅₄ plates(EMD Chemicals) and visualizing by UV (254 nm), 4% phosphomolybdic acid(PMA) in ethanol (EtOH), 4% ninhydrin in ethanol and/or using an iodinechamber. High performance liquid chromatography (HPLC) was performedusing a Waters 2695 Separations Module equipped with a Waters 2996Photodiode Array Detector and operated with Empower Pro software (WatersCorp.). Separations were carried out at 1 ml/min on a Restek Pinnacle DBC18 column (5 um, 4.6×150 mm) maintained at 30° C. Samples for HPLC wereprepared by dissolving 1 mg of sample in 1 ml mobile phase A:B (1:1) andinjecting 5 μL onto the column. The mobile phase consisted of A=0.1%trifluoroacetic acid (TFA) in water and B=0.1% TFA in acetonitrile (ACN)operated using gradient elution from 95:5 A:B to 5:95 A:B (gradient, 25min) followed by 100% B (isocratic, 5 min). Liquid chromatography/massspectrometry (LC-MS) was performed using a Finnigan Mat LCQ MassSpectrometer via direct infusion of samples (50 ppm) in methanol and thetotal ion count monitored using electrospray ionization in the (+) mode(ESI+). ¹H and ¹³C Nuclear magnetic resonance (NMR) spectroscopy wasperformed using a Eft-60 NMR Spectrometer (Anasazi instruments, Inc.)and processed using WinNuts software (Acorn NMR, Inc.). Melting pointswere determined using a Meltemp apparatus (Laboratory Devices). Puritywas determined by HPLC-UV/Vis.

General Procedure: Synthesis of Substituted Monoamines (3)

LC-MS Structure Purity (% Relative ID Chemical Name R₁ (%) Abundance) 3aN-(3,4-dimethoxybenzyl)-2- 3,4-dimethoxyphenyl 99.5 272.1 (100)phenylethanamine 3b N-(4-methoxybenzyl)-2- 4-methoxyphenyl 94.3 242.0(100) phenylethanamine 3c N-(3-phenoxybenzyl)-2- 3-phenoxyphenyl 99.5304.1 (100) phenylethanamine 3d N-(2,5-dimethoxybenzyl)-2-2,5-dimethoxyphenyl 99.1 272.1 (100) phenylethanamine 3eN-(3,4-dimethylbenzyl)-2- 3,4-dimethylphenyl 98.3 240.1 (100)phenylethanamine 3f N-(cyclohexylmethyl)-2- cyclohexyl 99.5 218.2 (100)phenylethanamine 3g N-(3,5-dimethoxybenzyl)-2- 3,5-dimethoxyphenyl 94.2272.1 (100) phenylethanamine

Aldehydes 1 (1 mmol) were added to solutions of phenethylamine 2 (181mg, 1.5 mmol) in methanol (MeOH) (2 mL) and the solutions stirred in asealed vessel at room temperature for 3 h to allow for imine formation.Polystyrene borohydride resin (PS—BH₃) (1 g, 2.5 mmol) was added and themixture stirred at room temperature (R.T.) for 16 h. The reactions weremonitored by TLC using 5% methanol in chloroform (CHCl₃) and PMAstaining until complete disappearance of the aldehydes. At this time,CHCl₃ (3 ml) was added, followed by polystyrene aldehyde resin (PS—CHO)(500 mg, 1.25 mmol) and the mixture stirred for 20 h. After completedisappearance of phenethylamine as monitored by TLC, the solids werefiltered off and washed with methanol (5 ml) and the solvents removedunder reduced pressure. The crude products were purified by flashchromatography on silica gel using the following (MeOH:CHCl₃)compositions: 3a, 3b, 3d, 3e, 3f (5:95); 3c, 3g (3:97). Product puritywas determined by HPLC and product identity confirmed by LC-MS (ESI+).

Specific Procedures: Synthesis of Miscellaneous Compounds

2-(3,4-dimethoxyphenyl)-N-phenethylethanamine (3h)-Phenethylamine 2 (222mg, 1.83 mmol) was added to a solution of 3,4-dimethoxyphenethylbromide4 (300 mg, 1.22 mmol) in DMF (3 ml) and the solution stirred at R.T. for4 h. At this time, TLC (5% methanol in chloroform) showed the completedisappearance of starting material and the formation of a major product.The solution was partitioned between t-butyl methyl ether (MTBE): 1Nsodium hydroxide (NaOH) (10 ml: 7 ml), separated and the organic layerwashed with saturated NaCl (10 ml), dried with Na₂SO₄ and the solventsremoved to give an oil. The crude product was purified by flashchromatography using 5% methanol in chloroform. Identification of thedesired product [m/z [M₊H]⁺ 286.2 (100%)] was confirmed by LC-MSanalysis (ESI+) and purity (99.4%) was confirmed by HPLC analysis(λ_(max)@272 nm).

N-(3,4-dimethoxybenzyl)-N-methyl-2-phenylethanamine(7)—3,4-Dimethoxybenzaldehyde 5 (166 mg, 1 mmol) was added to a mixtureof polystyrene cyanoborohydride resin (PS—BH₃CN) (1 g, 2.5 mmol) in1,2-dichloroethylene (DCE) (3.7 ml), followed by N-methylphenethylamine6 (203 mg, 1.5 mmol) and glacial acetic acid (AcOH) (370 μl) and themixture stirred at R.T. for 16 h in a sealed vessel. At this time, TLC(5% methanol in chloroform) showed the clean formation of product.Silica gel-bound propionyl chloride (SG-COCl) (545 mg, 0.6 mmol) wasadded followed by DCE (3 ml) and the mixture stirred for 20 h. At thistime, TLC showed the complete disappearance of N-methylphenethylamine.The solids were filtered off and washed with methanol (5 ml) and thesolvents removed under reduced pressure. The crude product was purifiedby flash chromatography on silica gel using 3% MeOH in CHCl₃.Identification of the desired product [m/z [M+H]⁺ 286.2 (100%)] wasconfirmed by LC-MS analysis (ESI+) and purity (99.5%) was confirmed byHPLC analysis (λ_(max)@272 nm).

N-(3,4-dimethoxybenzyl)-3-methylbutan-1-amine (9)—Isopropylethylamine 8(175 ul, 1.5 mmol) was added to a solution of 3,4-dimethoxybenzaldehyde5 (166 mg, 1 mmol) in MeOH (2 ml) and the solution stirred in a sealedvessel at R.T. for 3 h to allow for imine formation. Polystyreneborohydride resin (1 g, 2.5 mmol) was added and the mixture stirred atR.T. for 16 h. At this time, TLC (5% methanol in chloroform) showed theclean formation of product. Polystyrene aldehyde resin (500 mg, 1.25mmol) was added followed by CHCl₃ (3 ml) and the mixture stirred for 20h. At this time, TLC showed very small amounts of isopropylethylamine.The solids were filtered off and washed with methanol (5 ml) and thesolvents removed under reduced pressure. The crude product was purifiedby flash chromatography on silica gel using 8% MeOH in CHCl₃.Identification of the desired product [m/z [M+H]⁺ 238.0 (100%)] wasconfirmed by LC-MS analysis (ESI+) and purity (99.1%) was confirmed byHPLC analysis (λ_(max)@272 nm).

Skin Care Compositions

Compositions of this invention also include a cosmetically acceptablecarrier. Amounts of the carrier may range from about 1 to about 99.9%,preferably from about 70 to about 95%, optimally from about 80 to about90% by weight of the composition. Among the useful carriers are water,emollients, fatty acids, fatty alcohols, humectants, thickeners andcombinations thereof. The carrier may be aqueous, anhydrous or anemulsion. Preferably the compositions are aqueous, especially water andoil emulsions of the W/O or O/W or triplex W/O/W variety. Water whenpresent may be in amounts ranging from about 5 to about 95%, preferablyfrom about 20 to about 70%, optimally from about 35 to about 60% byweight.

Emollient materials may serve as cosmetically acceptable carriers. Thesemay be in the form of silicone oils, synthetic esters and hydrocarbons.Amounts of the emollients may range anywhere from about 0.1 to about95%, preferably between about 1 and about 50% by weight of thecomposition.

Silicone oils may be divided into the volatile and nonvolatile variety.The term “volatile” as used herein refers to those materials which havea measurable vapor pressure at ambient temperature. Volatile siliconeoils are preferably chosen from cyclic (cyclomethicone) or linearpolydimethylsiloxanes containing from 3 to 9, preferably from 4 to 5,silicon atoms.

Nonvolatile silicone oils useful as an emollient material includepolyalkyl siloxanes, polyalkylaryl siloxanes and polyether siloxanecopolymers. The essentially nonvolatile polyalkyl siloxanes usefulherein include, for example, polydimethyl siloxanes with viscosities offrom about 5×10⁻⁶ to 0.1 m²/s at 25° C. Among the preferred nonvolatileemollients useful in the present compositions are the polydimethylsiloxanes having viscosities from about 1×10⁻⁵ to about 4×10⁻⁴ m²/s at25° C.

Another class of nonvolatile silicones are emulsifying andnon-emulsifying silicone elastomers. Representative of this category isDimethicone/Vinyl Dimethicone Crosspolymer available as Dow Corning9040, General Electric SFE 839, and Shin-Etsu KSG-18. Silicone waxessuch as Silwax WS-L (Dimethicone Copolyol Laurate) may also be useful.

Among the ester emollients are:

1) Alkyl esters of saturated fatty acids having 10 to 24 carbon atoms.Examples thereof include behenyl neopentanoate, isononyl isonanonoate,isopropyl myristate and octyl stearate.

2) Ether-esters such as fatty acid esters of ethoxylated saturated fattyalcohols.

3) Polyhydric alcohol esters. Ethylene glycol mono and di-fatty acidesters, diethylene glycol mono- and di-fatty acid esters, polyethyleneglycol (200-6000) mono- and di-fatty acid esters, propylene glycol mono-and di-fatty acid esters, polypropylene glycol 2000 monostearate,ethoxylated propylene glycol monostearate, glyceryl mono- and di-fattyacid esters, polyglycerol poly-fatty esters, ethoxylated glycerylmono-stearate, 1,3-butylene glycol monostearate, 1,3-butylene glycoldistearate, polyoxyethylene polyol fatty acid ester, sorbitan fatty acidesters, and polyoxyethylene sorbitan fatty acid esters are satisfactorypolyhydric alcohol esters. Particularly useful are pentaerythritol,trimethylolpropane and neopentyl glycol esters of C₁-C₃₀ alcohols.

4) Wax esters such as beeswax, spermaceti wax and tribehenin wax.

5) Sugar ester of fatty acids such as sucrose polybehenate and sucrosepolycottonseedate.

Hydrocarbons which are suitable cosmetically acceptable carriers includepetrolatum, mineral oil, C₁₁-C₁₃ isoparaffins, and especiallyisohexadecane, available commercially as Permethyl 101A from PresperseInc.

Fatty acids having from 10 to 30 carbon atoms may also be suitable ascosmetically acceptable carriers. Illustrative of this category arepelargonic, lauric, myristic, palmitic, stearic, isostearic, oleic,hydroxystearic and behenic acids.

Fatty alcohols having from 10 to 30 carbon atoms are another usefulcategory of cosmetically acceptable carrier. Illustrative of thiscategory are stearyl alcohol, lauryl alcohol, myristyl alcohol and cetylalcohol.

Humectants of the polyhydric alcohol-type can be employed ascosmetically acceptable carriers. Typical polyhydric alcohols includeglycerol, polyalkylene glycols and more preferably alkylene polyols andtheir derivatives, including propylene glycol, dipropylene glycol,polypropylene glycol, polyethylene glycol and derivatives thereof,sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol,isoprene glycol, 1,2,6-hexanetriol, ethoxylated glycerol, propoxylatedglycerol and mixtures thereof. The amount of humectant may rangeanywhere from 0.5 to 50%, preferably between 1 and 15% by weight of thecomposition.

Thickeners can be utilized as part of the cosmetically acceptablecarrier of compositions according to the present invention. Typicalthickeners include crosslinked acrylates (e.g. Carbopol 982®),hydrophobically-modified acrylates (e.g. Carbopol 1382®), cellulosicderivatives and natural gums. Among useful cellulosic derivatives aresodium carboxymethylcellulose, hydroxypropyl methocellulose,hydroxypropyl cellulose, hydroxyethyl cellulose, ethyl cellulose andhydroxymethyl cellulose. Natural gums suitable for the present inventioninclude guar, xanthan, sclerotium, carrageenan, pectin and combinationsof these gums. Inorganics may also be utilized as thickeners,particularly clays such as bentonites and hectorites, fumed silicas, andsilicates such as magnesium aluminum silicate (Veegum®). Amounts of thethickener may range from 0.0001 to 10%, usually from 0.001 to 1%,optimally from 0.01 to 0.5% by weight of the composition.

Optional Ingredients

The inventive composition preferably includes an additional skinlightening compound, to obtain optimum skin lightening performance at anoptimum cost. Illustrative substances are placental extract, lacticacid, niacinamide, arbutin, kojic acid, ferulic acid, hydroquinone,resorcinol and derivatives including 4-substituted resorcinols andcombinations thereof. More preferably, such additional skin lighteningcompound is a tyrosinase inhibitor, to complement the melanogenesisinhibition activity of the substituted monoamines, most preferably acompound selected from the group consisting of kojic acid, hydroquinoneand 4-substituted resorcinol. Amounts of these agents may range fromabout 0.1 to about 10%, preferably from about 0.5 to about 2% by weightof the composition. It is preferred that the skin lightening coactiveaccording to the invention is vitamin B3 or a derivative thereof and isselected from the group consisting of niacinamide, nicotinic acidesters, non-vasodilating esters of nicotinic acid, nicotinyl aminoacids, nicotinyl alcohol esters of carboxylic acids, nicotinic acidN-oxide, niacinamide N-oxide and mixtures thereof.

Sunscreen is another preferred ingredient of the inventive compositionsParticularly preferred are such materials as ethylhexylp-methoxycinnamate (available as Parsol MCV®), Avobenzene (available asParsol 1789®), octylsalicylate (available as Dermablock OS®),tetraphthalylidene dicamphor sulfonic acid (available as Mexoryl SX®),benzophenone-4 and benzophenone-3 (Oxybenzone). Inorganic sunscreenactives may be employed such as microfine titanium dioxide, zinc oxide,polyethylene and various other polymers. By the term “microfine” ismeant particles of average size ranging from about 10 to about 200 nm,preferably from about 20 to about 100 nm. Amounts of the sunscreenagents when present may generally range from 0.1 to 30%, preferably from2 to 20%, optimally from 4 to 10% by weight of the composition.

More preferred inventive compositions include both the additional skinlightening compound, especially tyrosinase inhibitor, and a sunscreencompound.

Another preferred ingredient of the inventive compositions is aretinoid. As used herein, “retinoid” includes all natural and/orsynthetic analogs of Vitamin A or retinol-like compounds which possessthe biological activity of Vitamin A in the skin as well as thegeometric isomers and stereoisomers of these compounds. The retinoid ispreferably retinol, retinol esters (e.g., C2-C22 alkyl esters ofretinol, including retinyl palmitate, retinyl acetate, retinylpropionate), retinal, and/or retinoic acid (including all-trans retinoicacid and/or 13-cis-retinoic acid), more preferably retinoids other thanretinoic acid. These compounds are well known in the art and arecommercially available from a number of sources, e.g., Sigma ChemicalCompany (St. Louis, Mo.), and Boerhinger Mannheim (Indianapolis, Ind.).Other retinoids which are useful herein are described in U.S. Pat. Nos.4,677,120, issued Jun. 30, 1987 to Parish et al.; U.S. Pat. No.4,885,311, issued Dec. 5, 1989 to Parish et al.; U.S. Pat. No.5,049,584, issued Sep. 17, 1991 to Purcell et al.; U.S. Pat. No.5,124,356, issued Jun. 23, 1992 to Purcell et al.; and U.S. Pat. No.Reissue 34,075, issued Sep. 22, 1992 to Purcell et al. Other suitableretinoids are tocopheryl-retinoate [tocopherol ester of retinoic acid(trans- or cis-), adapalene{6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid}, and tazarotene(ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)-ethynyl]nicotinate).Preferred retinoids are retinol, retinyl palmitate, retinyl acetate,retinyl propionate, retinal and combinations thereof. The retinoid ispreferably substantially pure, more preferably essentially pure. Thecompositions of this invention may contain a safe and effective amountof the retinoid, such that the resultant composition is safe andeffective for regulating keratinous tissue condition, preferably forregulating visible and/or tactile discontinuities in skin, morepreferably for regulating signs of skin aging, even more preferably forregulating visible and/or tactile discontinuities in skin textureassociated with skin aging. The compositions preferably contain from orabout 0.005% to or about 2%, more preferably 0.01% to or about 2%,retinoid. Retinol is preferably used in an amount of from or about 0.01%to or about 0.15%; retinol esters are preferably used in an amount offrom or about 0.01% to or about 2% (e.g., about 1%); retinoic acids arepreferably used in an amount of from or about 0.01% to or about 0.25%;tocopheryl-retinoate, adapalene, and tazarotene are preferably used inan amount of from or about 0.01% to or about 2%.

Surfactants may also be present in compositions of the presentinvention. Total concentration of the surfactant when present may rangefrom about 0.1 to about 40%, preferably from about 1 to about 20%,optimally from about 1 to about 5% by weight of the composition. Thesurfactant may be selected from the group consisting.of anionic,nonionic, cationic and amphoteric actives. Particularly preferrednonionic surfactants are those with a C₁₀-C₂₀ fatty alcohol or acidhydrophobe condensed with from 2 to 100 moles of ethylene oxide orpropylene oxide per mole of hydrophobe; C₂-C₁₀ alkyl phenols condensedwith from 2 to 20 moles of alkylene oxide; mono- and di-fatty acidesters of ethylene glycol; fatty acid monoglyceride; sorbitan, mono- anddi-C₈-C₂₀ fatty acids; and polyoxyethylene sorbitan as well ascombinations thereof. Alkyl polyglycosides and saccharide fatty amides(e.g. methyl gluconamides) are also suitable nonionic surfactants.

Preferred anionic surfactants include soap, alkyl ether sulfates andsulfonates, alkyl sulfates and sulfonates, alkylbenzene sulfonates,alkyl and dialkyl sulfosuccinates, C₈-C₂₀ acyl isethionate, C₈-C₂₀ alkylether phosphates, C₈-C₂₀ sarcosinates and combinations thereof.

Preservatives can desirably be incorporated into the cosmeticcompositions of this invention to protect against the growth ofpotentially harmful microorganisms. Suitable traditional preservativesfor compositions of this invention are alkyl esters ofpara-hydroxybenzoic acid. Other preservatives which have more recentlycome into use include hydantoin derivatives, propionate salts, and avariety of quaternary ammonium compounds. Cosmetic chemists are familiarwith appropriate preservatives and routinely choose them to satisfy thepreservative challenge test and to provide product stability.Particularly preferred preservatives are phenoxyethanol, methyl paraben,propyl paraben, imidazolidinyl urea, sodium dehydroacetate and benzylalcohol. The preservatives should be selected having regard for the useof the composition and possible incompatibilities between thepreservatives and other ingredients in the emulsion. Preservatives arepreferably employed in amounts ranging from 0.01% to 2% by weight of thecomposition.

Compositions of the present invention may include vitamins. Illustrativevitamins are Vitamin A (retinol), Vitamin B₂, Vitamin B₃ (niacinamide),Vitamin B₆, Vitamin B12, Vitamin C, Vitamin D, Vitamin E, Vitamin K andBiotin. Derivatives of the vitamins may also be employed. For instance,Vitamin C derivatives include ascorbyl tetraisopalmitate, magnesiumascorbyl phosphate and ascorbyl glycoside. Derivatives of Vitamin Einclude tocopheryl acetate, tocopheryl palmitate and tocopheryllinoleate. DL-panthenol and derivatives may also be employed. Aparticularly suitable Vitamin B₆ derivative is pyridoxine palmitate.Flavonoids may also be useful, particularly glucosyl hesperidin, rutin,and soy isoflavones (including genistein, daidzein, equol, and theirglucosyl derivatives) and mixtures thereof. Total amount of vitamins orflavonoids when present may range from 0.0001 to 10%, preferably from0.01% to 1%, optimally from 0.1 to 0.5% by weight of the composition.

Another type of useful substance can be that of an enzyme such asoxidases, proteases, lipases and combinations. Particularly preferred issuperoxide dismutase, commercially available as Biocell SOD from theBrooks Company, USA.

Desquamation promoters may be present. Illustrative are themonocarboxylic acids. Monocarboxylic acids may be substituted orunsubstituted with a carbon chain length of up to 16. Particularlypreferred carboxylic acids are the alpha-hydroxycarboxylic acids,beta-hydroxycarboxylic or polyhydroxycarboxylic acids. The term “acid”is meant to include not only the free acid but also salts and C₁-C₃₀alkyl or aryl esters thereof and lactones generated from removal ofwater to form cyclic or linear lactone structures. Representative acidsare glycolic, lactic malic and tartaric acids. A representative saltthat is particularly preferred is ammonium lactate Salicylic acid isrepresentative of the beta-hydroxycarboxylic acids. Amounts of thesematerials when present may range from about 0.01 to about 15% by weightof the composition. Other phenolic acids include ferulic acid, salicylicacid, kojic acid and their salts.

Dicarboxylic acids represented by the formula HOOC-(CxHy)-COOH where x=4to 20 and y=6 to 40 such as azelaic acid, sebacic acid, oxalic acid,succinic acid, fumaric acid, octadecenedioic acid or their salts or amixture thereof.

A variety of herbal extracts may optionally be included in compositionsof this invention. Illustrative are pomegranate, white birch (BetulaAlba), green tea, chamomile, licorice and extract combinations thereof.The extracts may either be water soluble or water-insoluble carried in asolvent which respectively is hydrophilic or hydrophobic. Water andethanol are the preferred extract solvents.

Also included may be such materials as resveratrol, alpha-lipoic acid,ellagic acid, kinetin, retinoxytrimethylsilane (available from ClariantCorp. under the Silcare 1M-75 trademark), dehydroepiandrosterone (DHEA)and combinations thereof. Ceramides (including Ceramide 1, Ceramide 3,Ceramide 3B, Ceramide 6 and Ceramide 7) as well as pseudoceramides mayalso be utilized for many compositions of the present invention but mayalso be excluded. Amounts of these materials may range from about0.000001 to about 10%, preferably from about 0.0001 to about 1% byweight of the composition.

Colorants, opacifiers and abrasives may also be included in compositionsof the present invention. Each of these substances may range from about0.05 to about 5%, preferably between 0.1 and 3% by weight of thecomposition.

The compositions of the present invention may contain a safe andeffective amount of a peptide active selected from pentapeptides,derivatives of pentapeptides, and mixtures thereof. As used herein,“pentapeptides” refers to both the naturally occurring pentapeptides andsynthesized pentapeptides. Also useful herein are naturally occurringand commercially available compositions that contain pentapeptides. Apreferred commercially available pentapeptide derivative-containingcomposition is Matrixyl®, which is commercially available from Sederma,France. The pentapeptides and/or pentapeptide derivatives are preferablyincluded in amounts of from about 0.000001% to about 10%, morepreferably from about 0.000001% to about 0.1%, even more preferably fromabout 0.00001% to about 0.01%, by weight of the composition. Inembodiments wherein the pentapeptide-containing composition, Matrixyl®,is used, the resulting composition preferably contains from about 0.01%to about 50%, more preferably from about 0.05% to about 20%, and evenmore preferably from about 0.1% to about 10%, by weight of the resultingcomposition, of Matrixyl®.

Additional peptides, including but not limited to, di-, tri-, andtetrapeptides and derivatives thereof, and poly amino acid sequences ofmolecular weight from 200-20000. Amino acids may be naturally occurringor synthetic, dextro or levo, straight chain or cyclized and may beincluded in the compositions of the present invention in amounts thatare safe and effective. As used herein, “peptides” refers to both thenaturally occurring peptides and synthesized peptides. Also usefulherein are naturally occurring and commercially available compositionsthat contain peptides.

Suitable dipeptides for use herein include Carnosine. Preferredtripeptides and derivatives thereof may be purchased as Biopeptide CL®and a copper derivative sold commercially as lamin, from Sigma (St.Louis, Mo.).

Skin moisturizers, e,g. hyaluronic acid and/or its precursor N-acetylglucosamine may be included. N-acetyl glucosamine may be found in sharkcartilage or shitake mushrooms and are available commercially fromMaypro Industries, Inc (New York).

Anti-perspirants/deodorants skin care products of the invention mayfurther include well known antiperspirant metal salts of aluminum, zinc,zirconium and zirconium aluminum mixtures of sulfates, chlorides,chlorohydroxides, tetrachlorohydrex glycinates, alums, formates,lactates, benzyl sulfonates, succinates, phenol sulfonates and the like.Typical levels of antiperspirant/deodorant agent are from about 0% toabout 35%, preferably from about 0% to about 25% by weight of thecomposition. The composition may further include a complexing agent suchas an organic acid or derivative thereof that are capable of formingcomplexes with the antiperspirant metallic salt. Examples of suchcomplexing agents include, but are not limited to acetic acid, propionicacid, oxalic acid, malonic acid, succinic acid, tartaric acid, glycineand the like together with their cosmetically acceptable salts. Typicallevels of complexing agent are from about 0% to about 15%, preferablyfrom about 0% to about 10%, by weight of the composition.

The composition of the invention may comprise a conventional deodorantbase as the cosmetically acceptable carrier. By a deodorant is meant aproduct in the stick, roll-on, or propellant medium which is used forpersonal deodorant benefit e.g. application in the under-arm area whichmay or may not contain anti-perspirant actives.

Deodorant compositions can generally be in the form of firm solids, softsolids, gels, creams, and liquids and are dispensed using applicatorsappropriate to the physical characteristics of the composition.

Deodorant compositions which are delivered through roll-ons generallycomprise a liquid carrier. Such liquid carrier can be hydrophobic orcomprise a mixture of both hydrophilic and hydrophobic liquids. They maybe in the form of an emulsion or a microemulsion. The liquid carrier ormixture of carriers often constitutes from 30 to 95% by weight of thecomposition and in many instances from 40 to 80%.

Hydrophobic liquid carriers commonly can comprise one or more materialsselected within the chemical classes of siloxanes, hydrocarbons,branched aliphatic alcohols, esters and ethers that have a melting pointnot higher than 25° C. and a boiling point of at least 100° C.

Hydrophilic carrier liquids that can be employed in compositions hereincommonly comprise water and/or a mono or polyhydric alcohol orwater-miscible homologue. Monohydric alcohols often are short chain, bywhich is meant that they contain up to 6 carbons, and in practice aremost often ethanol or sometimes iso-propanol. Polyhydric alcoholscommonly comprise ethylene or propylene glycol, or a homologue can beemployed such as diethylene glycol.

The compositions that remain in liquid form can be applied employingconventional applicators such as a roll-on or by being pumped orsqueezed through a spray-generating orifice. Such compositions may bethickened, for example using one or more thickeners describedsubsequently herein.

Compositions that are firm solids, commonly obtained by use of a gellantor structurant, can be applied employing a stick applicator and softsolids, gels and creams can be applied employing an applicator having adispensing head provided with at least one aperture through which thesoft solid, gel or cream can be extruded under mild pressure.

Suitable thickeners or gellants that may be used for achieving this isby use of water-soluble or dispersible materials of higher viscosity,including various of the emulsifiers, and/or thickened or gelled withwater-soluble or water-dispersible polymers including polyacrylates, andwater-soluble or dispersible natural polymers, such as water-solublepolysaccharide or starch derivatives, such as alginates, carageenan,agarose and water-dispersible polymers include cellulose derivatives.

The concentration of such polymers in the water-immiscible liquid isoften selected in the range of from 1 to 20%, depending on the extent ofthickening or structuring required, and the effectiveness of the chosenpolymer in the liquid/mixture.

One class of structurant which is desirable by virtue of its longstanding proven capability to produce firm solids and more recently inmaking soft solids, comprises waxes. Herein, the term wax is employed toencompass not only materials of natural origin that are solid with awaxy feel and water-insoluble at 30-40° C., but melt at a somewhathigher temperature, typically between 50 and 95° C., such as beeswax,candelilla or carnauba wax, but also materials having similarproperties. Such other waxes include hydrocarbon waxes, e.g. paraffinwax, mineral wax and microcrystalline wax; synthetic waxes, such aspolyethylene of 2000 to 10000 daltons; waxy derivatives or waxycomponents of natural waxes

Mixtures of materials within each class of gellant/structurant can beemployed.

When the antiperspirant composition employed herein comprises an aerosolcomposition, it contains a propellant in addition to a base compositionas described herein above, commonly in a weight ratio of from 95:5 to40:60, and in many formulations, the weight ratio is from 90:10 to50:50.

The propellant is conveniently a low boiling point material, typicallyboiling below −5° C., for example an alkane such as propane, butane orisobutane, and possibly containing a fraction of pentane or isopentane,or a hydrofluorocarbon or fluorocarbon of similar carbon content. Duringfilling of the aerosol canister, the propellant gas is liquified byvirtue of the elevated pressure that is generated therein.

Examples of a hardening agent useful in the skin care compositions ofthe present invention include, but are not limited to lower alkanolamines, diamines and amides wherein such materials comprise at least twolower alkanol groups, preferably from about two to about four loweralkanol groups having from about 2 to about 4 carbon atoms. Examples ofsuch hardening agents include, but are not limited totetrahydroxyalkyldiamine compounds such astetrahydroxypropylethylenediamine, polyoxamine compounds such aspolyoxyethylene, polyoxypropylene block copolymers of ethylenediamineand alkanolamide compounds such as coconut diethanolamide and laurylmonoethanolamide. Typical levels of hardening agent are from about 0% toabout 5% by weight of the composition.

Further ingredients useful in skin care compositions herein may beselected from any and all: skin conditioning agents, skin feel mildnessagents, suspending agents, auxiliary thickening agents, viscositycontrol agents, dispersants, solubilizing/clarifying agents,stabilizers, opacifiers/pearlescent agents, chelating/sequesteringagents, hydrotropes, bactericides/fungicides, antioxidants, pH controlagents, buffering agents, colorants and perfumes/fragrances, water,other optional ingredients (auxilary agents) and the like.

The compositions of the present invention can also be optionally,incorporated into a water insoluble substrate for application to theskin such as in the form of a treated wipe.

While the above summarizes the present invention, it will becomeapparent to those skilled in the art that modifications, variations andalterations may be made without deviating from the scope and spirit ofthe present invention as described and claimed herein. The inventionwill now be further illustrated in the following non-limiting examples.

EXAMPLE 1

Various representative substituted monoamines of Structure I within thescope of the invention were investigated for inhibition of melanogenesisactivity.

Melanoderm tissue equivalent model MEL-300 (MatTek: Ashland, Mass.)containing melanocytes obtained from dark skin individuals were culturedas per supplier instructions. Components were added to the maintenancemedium phase (no topical treatments) at a final concentration of 10 μMfor 14 days at which time the experiment was terminated and the tissuesassessed for melanin content. Medium and treatments were changed threetimes per week. DMSO was utilized as the vehicle control and alltreatments were performed at least in duplicate.

For quantification of total melanin, each Melanoderm was placed into anindividual Eppendorf tube (2 mL) into which 250 μL of Solvable™ tissuesolubilizer (Packard Bioscience Co., Cat #6NE9100) was added. Each tubewas vortexed and incubated at 60° C. for 18 hours. Each sample was thencentrifuged (5-minutes at 13,000 RPMs) to remove any particulates. 100or 200 μL of supernatant were transferred to a 96 well microtiter plateand the absorbance read at 490 nm. Total melanin content was calculatedfrom a standard curve using synthetic melanin (Sigma Cat #M8631). Datawas analyzed for significance using the t-test in Microsoft Excel togenerate p-values (p-values less than 0.01 represent 99% confidence, pvalues of 0.05 represent 95% confidence both of which are statisticallysignificant).

The results that were obtained are summarized in Table 1. The resultsshow that compounds included in this invention inhibit melanogenesis.

TABLE 1 Melanoderm (% Reduction Compound ID Structure at 10 μM) p value3a

40.3 0.0116 3b

54.4 0.0065 3c

68.9 0.0040 3d

60.3 0.0051 3e

64.5 0.0046 3f

69.5 0.0040 3g

51.6 0.0069 3h

53.1 0.0066 7

44.4 0.0096

COMPARATIVE EXAMPLE 2

This example investigated structural criticalities of the compoundswithin the invention.

Melanoderm (% Reduction Compound ID Structure at 10 μM) p value 9

1.9 0.4510It can be seen from comparing Compound 3a in Table 1 (within the scopeof the invention) to Compound 9 in Example 2 (outside the scope of theinvention) that the terminal phenyl ring is critical for inhibition ofmelanogenesis activity.

EXAMPLE 3

The following skin lightening product is prepared according to theinvention:

INGREDIENT % composition by weight Water q.s. to 100 Stearic acid 18.00Cetyl alcohol 0.40 Glyceryl monostearate 0.60 Silicone oil 0.50 Sodiumcetostearyl sulphate 1.0 Mixture of sorbitan esters and 1.5 ethoxylatedfatty acid esters Alkyl acrylate cross polymer 0.15 Polyhydric alcohol10.00 Preservatives 0.5 Niacinamide 1.00 Inventive compound 3f 2.00Parsol MCX 0.4 Benzophenones 0.75 Titanium dioxide 0.6

EXAMPLE 4

Skin care products within the scope of the invention are prepared:

Component A B C D Disodium EDTA 0.100 0.100 0.100 01.00 InventiveCompound 3f 2.000 0 1 0 Inventive Compound 3b 0 2.000 0 1 Methylsulfonyl methane 0 0 2.000 0 Niacinamide 4.000 4.000 4.000 5.000Octadecenedioic acid 0 0 0 2.000 Isohexadecane 3.000 3.000 3.000 3.000Isopropyl isostearate 1.330 1.330 1.330 1.330 Sucrose polycottonseedate0.670 0.670 0.670 0.670 Polymethylsilsesquioxane 0.250 0.250 0.250 0.250Cetearyl glucoside + cetearyl 0.200 0.200 0.200 0.200 alcohol Behenylalcohol 0.400 0.400 0.400 0.400 Ethylparaben 0.200 0.200 0.200 0.200Propylparaben 0.100 0.100 0.100 0.100 Cetyl alcohol 0.320 0.320 0.3200.320 Stearyl alcohol 0.480 0.480 0.480 0.480 Tocopheryl acetate 0.5000.500 0.500 0.500 PEG-100 stearate 0.100 0.100 0.100 0.100 Glycerin7.000 7.000 7.000 10.000 Titanium dioxide 0.604 0.604 0.604 0.604Polyacrylamide + C13-14 2.000 2.000 2.000 2.000 isoparaffin + laureth-7Panethenol 1.000 1.000 1.000 1.000 Benzyl alcohol 0.400 0.400 0.4000.400 Dimethicone + dimethiconol 2.000 2.000 2.000 2.000 Water (to 100g) to 100 to 100 to 100 To 100 Total 100 100 100 100

The water phase ingredients were combined in a suitable vessel andheated to 75° C. In a separate suitable vessel, combine the oil phaseingredients and heat to 75° C. Next add the oil phase to the water phaseand mill the resulting emulsion (e.g., with a Tekmar™ T-25 mill). Then,add the thickener to the emulsion and cool the emulsion to 45° C. whilestirring. At 45° C., add the remaining ingredients. Cool the product andstir to 30° C. and pour into suitable containers. The compositions arechronically applied topically to areas of hyperpigmented skin.

EXAMPLE 5

A representative skin care composition of the present invention in theform of a cosmetic lotion is outlined below:

INGREDIENT WEIGHT % Water Balance Disodium EDTA 0.05 Methyl Paraben 0.15Magnesium Aluminum Silicate 0.60 Triethanolamine 1.20 Inventive compound3f 1.00 Xanthan Gum 0.20 Natrosol ® 250HHR (ethyl cellulose) 0.50Butylene Glycol 3.00 Glycerin 2.00 Sodium Stearoyl Lactylate 0.10Glycerol Monostearate 1.50 Stearyl Alcohol 1.50 Isostearyl Palmitate3.00 Silicone Fluid 1.00 Cholesterol 0.25 Sorbitan Stearate 1.00Butylated Hydroxy Toluene 0.05 Vitamin E Acetate 0.01 PEG-100 Stearate2.00 Stearin Acid 3.00 Propyl Paraben 0.10 Parsol MCX ® 2.00Caprylic/Capric Triglyceride 0.50 Hydroxycaprylic Acid 0.01 C12-15 AlkylOctanoate 3.00 (Isotridecyloxy)propionic acid (branched) 2.00 or(Isotridecyloxy)acetic acid (branched) Vitamin A Palmitate 0.10Bisabolol 0.01 Vitamin A Acetate 0.01 Fragrance (20% Limonene and 3%gamma 0.03 terpinene) Retinol 50C 0.02

EXAMPLE 6

A water-in-oil topical liquid make-up foundation according to inventionis described:

INGREDIENT WEIGHT % (Isotridecyloxy)propionic acid (branched) 2.00 or(Isotridecyloxy)acetic acid (branched) Cyclomethicone 9.25 Oleyl Oleate2.00 Dimethicone Copolyol 20.00 Talc 3.38 Pigment (Iron Oxides) 10.51Spheron L-1500 (Silica) 0.50 Synthetic Wax Durachem 0602 0.10 ArachidylBehenate 0.30 Cyclomethicone 1.00 Trihydroxystearin 0.30 Laureth-7 0.50Propyl Paraben 0.25 Perfume 0.1 Water balance Inventive compound 3b 3.00Methyl Paraben 0.12 Propylene Glycol 8.00 Niacinamide 4.00 Glycerin 3.00Sodium Chloride 2.00 Sodium Dehydroacetate 0.30

EXAMPLE 7

An aerosol packaged foaming cleanser is outlined:

INGREDIENT WEIGHT % Sunflower Seed Oil 10.00 Glycerin 10.00 MaleatedSoybean Oil 5.00 Silicone Urethane 1.00 Polyglycero-4 Oleate 1.00 SodiumC14-16 Olefin Sulfonate 15.00 Sodium Lauryl Ether Sulphate (25% active)15.00 Cocoamidopropylbetaine 15.00 DC 1784 ® (Silicone Emulsion 50%)5.00 Polyquaternium-11 1.00 Inventive compound 3f 1.00 Fragrance (20%Limonene) 1.00 Water Balance

EXAMPLE 8

A toilet bar illustrative of the present invention is outlined:

INGREDIENT WEIGHT % Sodium Soap (85/15 Tallow/Coconut) 77.77 Inventivecompound 3e 3.50 Dimethicone 2.00 Sodium Chloride 0.77 Titanium Dioxide0.40 Ethylene Brassylate 1.50 Disodium EDTA 0.02 Sodium Etidronate 0.02Fluorescer 0.024 Water Balance

EXAMPLE 9

A shampoo composition useful in the context of the present invention isdescribed:

INGREDIENT WEIGHT % Ammonium Laureth Sulfate 12.00 Ammonium LaurylSulfate 2.00 Cocoamidopropyl Betaine 2.00 Sodium Lauroamphoacetate 2.00Glycerin 12.00 Inventive Compound 7 5.50 Ethylene Glycol Distearate 1.50Cocomonoethanolamide 0.80 Cetyl Alcohol 0.60 Polyquaternium-10 0.50Dimethicone 1.00 Zinc Pyridinethione 1.00 Sodium Citrate 0.40 CitricAcid 0.39 Sodium Xylene Sulfonate 1.00 Fragrance (10% Limonene) 0.40Sodium Benzoate 0.25 Kathon CG ® 0.0008 Benzyl Alcohol 0.0225 WaterBalance

EXAMPLE 10

This Example illustrates an antiperspirant/deodorant formulaincorporating the substituted monoamine compound according to thepresent invention.

Ingredient Weight % (Isotridecyloxy)propionic acid (branched) 2.00Cyclopentasiloxane 39 Dimethicone 20 Aluminum Zirconium TrichlorohydrexGlycinate 15 Inventive Compound 7 5.0 C18-C36 Acid Triglyceride 5.0Microcrystalline Wax 3.0 Glycerin 8.0 Silica 2.5 DimethiconeCrosspolymer 1.0 Ethylene Brassylate 0.5 Disodium EDTA 0.4 ButylatedHydroxytoluene 0.3 Citric Acid 0.3While described in terms of the presently preferred embodiments, it isto be understood that such disclosure is not to be interpreted aslimiting. Various modifications and alterations will no doubt occur toone skilled in the art after having read the above disclosure.Accordingly, it is intended that the appended claims be interpreted ascovering all such modifications and alterations as falling within thetrue spirit and scope of the invention.

1. A skin lightening water and oil emulsion comprising: (a) from about0.001% to about 20% of a substituted monoamine of structure I:

wherein R₁ is selected from the group consisting of cyclohexyl, phenyl,mono- and di-substituted phenyl wherein the mono- and di-substitutionsare independently selected from the group consisting of: C₁-C₅ alkyl,C₁-C₅ alkoxy, and phenoxy; and R₂ is selected from the group consistingof hydrogen and methyl; (b) an additional skin lightening activeselected from the group consisting of placental extract, lactic acid,niacinamide, arbutin, kojic acid, ferulic acid, hydroxyquinone,resorcinol and 4-substituted resorcinols, and (c) a cosmeticallyacceptable carrier selected from the group consisting of water,emollients, fatty acids, fatty alcohols, humectants, thickeners andcombinations thereof.
 2. The composition of claim 1, wherein R₁ is mono-or di-substituted phenyl wherein the mono- and di-substitutions areindependently selected from the group consisting of methyl, ethyl,methoxy, and phenoxy; and R₂ is selected from the group consisting ofhydrogen and methyl.
 3. The composition of claim 1, wherein R₂ ishydrogen.
 4. The composition of claim 1 further comprising an ingredientselected from the group consisting of alpha-hydroxy acids,beta-hydroxyacids, tyrosinase inhibitors, organic sunscreens, inorganicsunscreens, vitamins, retinol, retinyl esters, peptides,N-acetylglucosamines, anti-inflammatories, and anti-oxidants.
 5. Thecomposition of claim 1 further comprising an anti-perspirant active. 6.The composition of claim 1 further comprising a surfactant.
 7. A methodof lightening skin, the method comprising applying to the skin thecomposition of claim 1.